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Q9BY41 (HDAC8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histone deacetylase 8

Short name=HD8
EC=3.5.1.98
Gene names
Name:HDAC8
Synonyms:HDACL1
ORF Names:CDA07
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length377 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. Ref.1 Ref.2 Ref.3 Ref.12 Ref.17

Catalytic activity

Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.

Cofactor

Binds 1 divalent metal cation per subunit.

Enzyme regulation

Its activity is inhibited by trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), 3-(1-methyl-4-phenylacetyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide (APHA), 4-dimethylamino-N-(6-hydroxycarbamoyethyl)benzamide-N-hydroxy-7-(4-dimethylaminobenzoyl)aminoheptanamide (MS-344), 5-(4-methyl-benzoylamino)-biphenyl-3,4'-dicarboxylic acid 3-dimethylamide 4'-hydroxyamide (CRA-A) and butyrate. Ref.18

Subunit structure

Interacts with PEPB2-MYH11, a fusion protein consisting of the 165 N-terminal residues of CBF-beta (PEPB2) with the tail region of MYH11 produced by the inversion Inv16(p13q22), a translocation associated with acute myeloid leukemia of M4EO subtype. The PEPB2-MYH1 fusion protein also interacts with RUNX1, a well known transcriptional regulator, suggesting that the interaction with HDAC8 may participate in the conversion of RUNX1 into a constitutive transcriptional repressor. Interacts with CBFA2T3. Interacts with phosphorylated SMG5/EST1B; this interaction protects SMG5 from ubiquitin-mediated degradation. Associates with alpha-SMA (smooth muscle alpha-actin). Ref.10 Ref.11 Ref.15

Subcellular location

Nucleus. Cytoplasm. Note: Excluded from the nucleoli. Found in the cytoplasm of cells showing smooth muscle differentiation. Ref.12 Ref.13 Ref.14

Tissue specificity

Weakly expressed in most tissues. Expressed at higher level in heart, brain, kidney and pancreas and also in liver, lung, placenta, prostate and kidney. Ref.2 Ref.12 Ref.13 Ref.14

Post-translational modification

Phosphorylated by PKA on serine 39. Phosphorylation reduces deacetylase activity observed preferentially on histones H3 and H4. Ref.12 Ref.18

Involvement in disease

Cornelia de Lange syndrome 5 (CDLS5) [MIM:300882]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17

Wilson-Turner X-linked mental retardation syndrome (WTS) [MIM:309585]: A neurologic disorder characterized by severe intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Affected females have a milder phenotype than affected males.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16

Sequence similarities

Belongs to the histone deacetylase family. HD type 1 subfamily.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Mental retardation
Obesity
   LigandMetal-binding
   Molecular functionChromatin regulator
Hydrolase
Repressor
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchromatin assembly or disassembly

Traceable author statement Ref.1. Source: ProtInc

chromatin modification

Traceable author statement PubMed 12711221. Source: UniProtKB

mitotic cell cycle

Traceable author statement. Source: Reactome

negative regulation of transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

regulation of cohesin localization to chromatin

Inferred from mutant phenotype Ref.17. Source: UniProtKB

sister chromatid cohesion

Inferred from mutant phenotype Ref.17. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Traceable author statement PubMed 12711221. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

histone deacetylase complex

Traceable author statement PubMed 12711221. Source: UniProtKB

nuclear chromosome

Traceable author statement Ref.1. Source: ProtInc

nucleus

Traceable author statement PubMed 12711221. Source: UniProtKB

   Molecular_functionNAD-dependent histone deacetylase activity (H3-K14 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H3-K18 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H3-K9 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H4-K16 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

histone deacetylase activity

Traceable author statement PubMed 12711221. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

transcription factor binding

Traceable author statement PubMed 12711221. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BY41-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9BY41-2)

The sequence of this isoform differs from the canonical sequence as follows:
     248-272: LKEVYQAFNPKAVVLQLGADTIAGD → RTSCPKSRPVEAAAAACLPHLHSLV
     273-377: Missing.
Note: Derived from EST data.
Isoform 3 (identifier: Q9BY41-3)

The sequence of this isoform differs from the canonical sequence as follows:
     147-163: DEASGFCYLNDAVLGIL → RDVCVCGTLQGILKKSK
     164-377: Missing.
Isoform 4 (identifier: Q9BY41-4)

The sequence of this isoform differs from the canonical sequence as follows:
     56-146: Missing.
Note: No experimental confirmation available.
Isoform 5 (identifier: Q9BY41-5)

The sequence of this isoform differs from the canonical sequence as follows:
     246-272: SVLKEVYQAFNPKAVVLQLGADTIAGD → RYEPPAPNPGL
     273-377: Missing.
Note: No experimental confirmation available.
Isoform 6 (identifier: Q9BY41-6)

The sequence of this isoform differs from the canonical sequence as follows:
     56-146: Missing.
     185-210: Missing.
     246-256: SVLKEVYQAFN → RYEPPAPNPGL
     257-377: Missing.
Note: Gene prediction based on EST data.
Isoform 7 (identifier: Q9BY41-7)

The sequence of this isoform differs from the canonical sequence as follows:
     147-158: DEASGFCYLNDA → ETCVYVALYKAF
     159-377: Missing.
Note: Gene prediction based on EST data.
Isoform 8 (identifier: Q9BY41-8)

The sequence of this isoform differs from the canonical sequence as follows:
     147-377: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 377377Histone deacetylase 8
PRO_0000114708

Regions

Region14 – 324311Histone deacetylase

Sites

Active site1431Proton acceptor Ref.20
Metal binding1781Divalent metal cation
Metal binding1801Divalent metal cation
Metal binding2671Divalent metal cation
Binding site1011Substrate
Binding site1511Substrate; via carbonyl oxygen
Binding site3061Substrate

Amino acid modifications

Modified residue391Phosphoserine Ref.18

Natural variations

Alternative sequence56 – 14691Missing in isoform 4 and isoform 6.
VSP_043426
Alternative sequence147 – 377231Missing in isoform 8.
VSP_047502
Alternative sequence147 – 16317DEASG…VLGIL → RDVCVCGTLQGILKKSK in isoform 3.
VSP_007174
Alternative sequence147 – 15812DEASG…YLNDA → ETCVYVALYKAF in isoform 7.
VSP_046832
Alternative sequence159 – 377219Missing in isoform 7.
VSP_046833
Alternative sequence164 – 377214Missing in isoform 3.
VSP_007175
Alternative sequence185 – 21026Missing in isoform 6.
VSP_046834
Alternative sequence246 – 27227SVLKE…TIAGD → RYEPPAPNPGL in isoform 5.
VSP_043427
Alternative sequence246 – 25611SVLKEVYQAFN → RYEPPAPNPGL in isoform 6.
VSP_046835
Alternative sequence248 – 27225LKEVY…TIAGD → RTSCPKSRPVEAAAAACLPH LHSLV in isoform 2.
VSP_007176
Alternative sequence257 – 377121Missing in isoform 6.
VSP_046836
Alternative sequence273 – 377105Missing in isoform 2 and isoform 5.
VSP_007177
Natural variant1801H → R in CDLS5. Ref.17
VAR_069140
Natural variant3111T → M in CDLS5. Ref.17
VAR_069141
Natural variant3201G → R in CDLS5. Ref.17
VAR_069142
Natural variant3341H → R in CDLS5. Ref.17
VAR_069143

Experimental info

Mutagenesis391S → A: Enhances the deacetylase activity. Ref.2 Ref.12
Mutagenesis391S → E: Decreases the deacetylase activity. Ref.2 Ref.12
Mutagenesis1011D → A: Complete loss of catalytical activity. Complete loss of catalytical activity; when associated with F-306. Ref.2 Ref.19 Ref.20
Mutagenesis1011D → E: Partial loss of catalytical activity. Ref.2 Ref.19 Ref.20
Mutagenesis1011D → L: Complete loss of catalytical activity. Ref.2 Ref.19 Ref.20
Mutagenesis1011D → N: Almost complete loss of catalytical activity. Ref.2 Ref.19 Ref.20
Mutagenesis142 – 1432HH → AA: Strongly reduces histone deacetylase activity. Ref.2 Ref.20
Mutagenesis1431H → A: Loss of catalytic activity. Ref.2 Ref.20
Mutagenesis3061Y → F: Loss of catalytic activity. Complete loss of catalytic activity; when associated with A-101. Ref.2 Ref.19
Sequence conflict311L → P in AAH50433. Ref.9
Sequence conflict1791L → V no nucleotide entry Ref.4
Sequence conflict2231R → W in AAF73428. Ref.2

Secondary structure

................................................................. 377
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 11, 2003. Version 2.
Checksum: CAA1B91894FB5013

FASTA37741,758
        10         20         30         40         50         60 
MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRIVKPK 

        70         80         90        100        110        120 
VASMEEMATF HTDAYLQHLQ KVSQEGDDDH PDSIEYGLGY DCPATEGIFD YAAAIGGATI 

       130        140        150        160        170        180 
TAAQCLIDGM CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFE RILYVDLDLH 

       190        200        210        220        230        240 
HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDVSDVGLG KGRYYSVNVP IQDGIQDEKY 

       250        260        270        280        290        300 
YQICESVLKE VYQAFNPKAV VLQLGADTIA GDPMCSFNMT PVGIGKCLKY ILQWQLATLI 

       310        320        330        340        350        360 
LGGGGYNLAN TARCWTYLTG VILGKTLSSE IPDHEFFTAY GPDYVLEITP SCRPDRNEPH 

       370 
RIQQILNYIK GNLKHVV 

« Hide

Isoform 2 [UniParc].

Checksum: 060E9B19659F4A91
Show »

FASTA27229,944
Isoform 3 [UniParc].

Checksum: 06E2B3E76A5D6B0D
Show »

FASTA16317,880
Isoform 4 [UniParc].

Checksum: B69361BAC77E90E2
Show »

FASTA28631,935
Isoform 5 [UniParc].

Checksum: 175AB23C2589926F
Show »

FASTA25628,353
Isoform 6 [UniParc].

Checksum: E46FD4F32AAABC43
Show »

FASTA13915,685
Isoform 7 [UniParc].

Checksum: F7EFADF18566BB00
Show »

FASTA15817,439
Isoform 8 [UniParc].

Checksum: 5234C861058EAE1B
Show »

FASTA14616,050

References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor."
Hu E., Chen Z., Fredrickson T., Zhu Y., Kirkpatrick R., Zhang G.-F., Johanson K., Sung C.-M., Liu R., Winkler J.
J. Biol. Chem. 275:15254-15264(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, FUNCTION.
Tissue: Kidney.
[2]"Cloning and characterization of a novel human histone deacetylase, HDAC8."
Buggy J.J., Sideris M.L., Mak P., Lorimer D.D., McIntosh B., Clark J.M.
Biochem. J. 350:199-205(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION, MUTAGENESIS OF 142-HIS-HIS-143.
Tissue: Uterus.
[3]"Cloning and characterization of human histone deacetylase 8."
Van den Wyngaert I., de Vries W., Kremer A., Neefs J.-M., Verhasselt P., Luyten W.H.M.L., Kass S.U.
FEBS Lett. 478:77-83(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, FUNCTION.
Tissue: Heart.
[4]"Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia."
McDonell N., Ramser J., Francis F., Vinet M.-C., Rider S., Sudbrak R., Riesselman L., Yaspo M.-L., Reinhardt R., Monaco A.P., Ross F., Kahn A., Kearney L., Buckle V., Chelly J.
Genomics 64:221-229(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]"Normalization and subtraction: two approaches to facilitate gene discovery."
Bonaldo M.F., Lennon G., Soares M.B.
Genome Res. 6:791-806(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8).
[6]"A novel gene expressed in human pheochromocytoma."
Li Y., Huang Q., Peng Y., Song H., Yu Y., Xu S., Ren S., Chen Z., Han Z.
Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Pheochromocytoma.
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5).
Tissue: Colon and Small intestine.
[8]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[10]"ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain."
Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., Downing J.R., Meyers S., Hiebert S.W.
Mol. Cell. Biol. 21:6470-6483(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBFA2T3.
[11]"The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain."
Durst K.L., Lutterbach B., Kummalue T., Friedman A.D., Hiebert S.W.
Mol. Cell. Biol. 23:607-619(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PEPB2-MYH11 FUSION PROTEIN.
[12]"Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent protein kinase A."
Lee H., Rezai-Zadeh N., Seto E.
Mol. Cell. Biol. 24:765-773(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY PKA, MUTAGENESIS OF SER-39, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[13]"Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility."
Waltregny D., Glenisson W., Tran S.L., North B.J., Verdin E., Colige A., Castronovo V.
FASEB J. 19:966-968(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[14]"Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus."
de Leval L., Waltregny D., Boniver J., Young R.H., Castronovo V., Oliva E.
Am. J. Surg. Pathol. 30:319-327(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[15]"Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation."
Lee H., Sengupta N., Villagra A., Rezai-Zadeh N., Seto E.
Mol. Cell. Biol. 26:5259-5269(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMG5.
[16]"X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face."
Harakalova M., van den Boogaard M.J., Sinke R., van Lieshout S., van Tuil M.C., Duran K., Renkens I., Terhal P.A., de Kovel C., Nijman I.J., van Haelst M., Knoers N.V., van Haaften G., Kloosterman W., Hennekam R.C., Cuppen E., Ploos van Amstel H.K.
J. Med. Genet. 49:539-543(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN WTS.
[17]"HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle."
Deardorff M.A., Bando M., Nakato R., Watrin E., Itoh T., Minamino M., Saitoh K., Komata M., Katou Y., Clark D., Cole K.E., De Baere E., Decroos C., Di Donato N., Ernst S., Francey L.J., Gyftodimou Y., Hirashima K. expand/collapse author list , Hullings M., Ishikawa Y., Jaulin C., Kaur M., Kiyono T., Lombardi P.M., Magnaghi-Jaulin L., Mortier G.R., Nozaki N., Petersen M.B., Seimiya H., Siu V.M., Suzuki Y., Takagaki K., Wilde J.J., Willems P.J., Prigent C., Gillessen-Kaesbach G., Christianson D.W., Kaiser F.J., Jackson L.G., Hirota T., Krantz I.D., Shirahige K.
Nature 489:313-317(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANTS CDLS5 ARG-180; MET-311; ARG-320 AND ARG-334.
[18]"Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases."
Somoza J.R., Skene R.J., Katz B.A., Mol C., Ho J.D., Jennings A.J., Luong C., Arvai A., Buggy J.J., Chi E., Tang J., Sang B.-C., Verner E., Wynands R., Leahy E.M., Dougan D.R., Snell G., Navre M. expand/collapse author list , Knuth M.W., Swanson R.V., McRee D.E., Tari L.W.
Structure 12:1325-1334(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEXES WITH TSA; SAHA; MS-344; CRA-A AND DIVALENT METAL CATION, ENZYME REGULATION, PHOSPHORYLATION AT SER-39.
[19]"Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex."
Vannini A., Volpari C., Gallinari P., Jones P., Mattu M., Carfi A., De Francesco R., Steinkuehler C., Di Marco S.
EMBO Rep. 8:879-884(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH DIVALENT METAL CATION, MUTAGENESIS OF ASP-101 AND TYR-306.
[20]"Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors."
Dowling D.P., Gantt S.L., Gattis S.G., Fierke C.A., Christianson D.W.
Biochemistry 47:13554-13563(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) IN COMPLEXES WITH PEPTIDE SUBSTRATE; SAHA; TSA; M-344 AND APHA, ACTIVE SITE, MUTAGENESIS OF ASP-101 AND HIS-143.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF230097 mRNA. Translation: AAF73076.1.
AF245664 mRNA. Translation: AAF73428.1.
AJ277724 mRNA. Translation: CAB90213.1.
BQ189619 mRNA. No translation available.
AK296641 mRNA. Translation: BAG59242.1.
AK300895 mRNA. Translation: BAG62534.1.
AA376331 mRNA. No translation available.
AI159768 mRNA. No translation available.
T99283 mRNA. No translation available.
AF212246 mRNA. Translation: AAK14930.1.
AL133500 Genomic DNA. No translation available.
BX295542 Genomic DNA. No translation available.
BC050433 mRNA. Translation: AAH50433.1.
CCDSCCDS14420.1. [Q9BY41-1]
CCDS55448.1. [Q9BY41-6]
CCDS55449.1. [Q9BY41-4]
CCDS55450.1. [Q9BY41-8]
CCDS55451.1. [Q9BY41-5]
CCDS55452.1. [Q9BY41-7]
RefSeqNP_001159890.1. NM_001166418.1. [Q9BY41-4]
NP_001159891.1. NM_001166419.1. [Q9BY41-5]
NP_001159892.1. NM_001166420.1. [Q9BY41-8]
NP_001159894.1. NM_001166422.1. [Q9BY41-7]
NP_001159920.1. NM_001166448.1. [Q9BY41-6]
NP_060956.1. NM_018486.2. [Q9BY41-1]
UniGeneHs.310536.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1T64X-ray1.90A/B1-377[»]
1T67X-ray2.31A1-377[»]
1T69X-ray2.91A1-377[»]
1VKGX-ray2.20A/B1-377[»]
1W22X-ray2.50A/B1-377[»]
2V5WX-ray2.00A/B1-377[»]
2V5XX-ray2.25A/B1-377[»]
3EW8X-ray1.80A1-377[»]
3EWFX-ray2.50A/B/C/D1-377[»]
3EZPX-ray2.65A/B1-377[»]
3EZTX-ray2.85A/B1-377[»]
3F06X-ray2.55A/B1-377[»]
3F07X-ray3.30A/B/C1-377[»]
3F0RX-ray2.54A/B/C1-377[»]
3MZ3X-ray3.20A/B1-377[»]
3MZ4X-ray1.84A/B1-377[»]
3MZ6X-ray2.00A1-377[»]
3MZ7X-ray1.90A1-377[»]
3RQDX-ray2.14A/B1-377[»]
3SFFX-ray2.00A1-377[»]
3SFHX-ray2.70A1-377[»]
ProteinModelPortalQ9BY41.
SMRQ9BY41. Positions 14-377.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120968. 94 interactions.
IntActQ9BY41. 16 interactions.
MINTMINT-5207407.
STRING9606.ENSP00000362674.

Chemistry

BindingDBQ9BY41.
ChEMBLCHEMBL3038483.
DrugBankDB02546. Vorinostat.
GuidetoPHARMACOLOGY2619.

PTM databases

PhosphoSiteQ9BY41.

Polymorphism databases

DMDM29839394.

Proteomic databases

MaxQBQ9BY41.
PaxDbQ9BY41.
PRIDEQ9BY41.

Protocols and materials databases

DNASU55869.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373554; ENSP00000362655; ENSG00000147099. [Q9BY41-8]
ENST00000373556; ENSP00000362657; ENSG00000147099. [Q9BY41-7]
ENST00000373559; ENSP00000362660; ENSG00000147099. [Q9BY41-6]
ENST00000373573; ENSP00000362674; ENSG00000147099. [Q9BY41-1]
ENST00000373589; ENSP00000362691; ENSG00000147099. [Q9BY41-4]
ENST00000439122; ENSP00000414486; ENSG00000147099. [Q9BY41-5]
ENST00000594004; ENSP00000469969; ENSG00000268498. [Q9BY41-8]
ENST00000599061; ENSP00000472489; ENSG00000268498. [Q9BY41-6]
ENST00000599422; ENSP00000472595; ENSG00000268498. [Q9BY41-4]
ENST00000600470; ENSP00000471156; ENSG00000268498. [Q9BY41-1]
ENST00000601791; ENSP00000471979; ENSG00000268498. [Q9BY41-5]
ENST00000601811; ENSP00000469214; ENSG00000268498. [Q9BY41-7]
GeneID55869.
KEGGhsa:55869.
UCSCuc004eau.3. human. [Q9BY41-1]
uc004eav.3. human. [Q9BY41-5]
uc011mqg.2. human. [Q9BY41-4]

Organism-specific databases

CTD55869.
GeneCardsGC0XM071549.
GeneReviewsHDAC8.
HGNCHGNC:13315. HDAC8.
HPAHPA048560.
MIM300269. gene.
300882. phenotype.
309585. phenotype.
neXtProtNX_Q9BY41.
Orphanet199. Cornelia de Lange syndrome.
3459. Wilson-Turner syndrome.
PharmGKBPA37766.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0123.
HOGENOMHOG000225180.
HOVERGENHBG057112.
InParanoidQ9BY41.
KOK11405.
OMACLIDGKC.
PhylomeDBQ9BY41.
TreeFamTF106175.

Enzyme and pathway databases

BRENDA3.5.1.98. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_21300. Mitotic M-M/G1 phases.
SABIO-RKQ9BY41.

Gene expression databases

ArrayExpressQ9BY41.
BgeeQ9BY41.
CleanExHS_HDAC8.
GenevestigatorQ9BY41.

Family and domain databases

Gene3D3.40.800.20. 1 hit.
InterProIPR000286. His_deacetylse.
IPR003084. His_deacetylse_1.
IPR023801. His_deacetylse_dom.
[Graphical view]
PANTHERPTHR10625. PTHR10625. 1 hit.
PfamPF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFPIRSF037913. His_deacetylse_1. 1 hit.
PRINTSPR01270. HDASUPER.
PR01271. HISDACETLASE.
ProtoNetSearch...

Other

ChiTaRSHDAC8. human.
EvolutionaryTraceQ9BY41.
GeneWikiHDAC8.
GenomeRNAi55869.
NextBio61182.
PROQ9BY41.
SOURCESearch...

Entry information

Entry nameHDAC8_HUMAN
AccessionPrimary (citable) accession number: Q9BY41
Secondary accession number(s): A6ND12 expand/collapse secondary AC list , A6ND61, A6NET3, A6NJR3, A8MQ62, B4DKN0, B4DV22, Q86VC8, Q9NP76, Q9NYH4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 11, 2003
Last sequence update: April 11, 2003
Last modified: July 9, 2014
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM